© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
L-Arginine inhibits smooth muscle cell proliferation of vein graft intimal thickness in hypercholesterolemic rabbits
Department of Surgery II, Faculty of Medicine, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812, Japan
* Corresponding author. Tel. (+81-92) 6425463; Fax. (+81-92) 6425482.
Received 4 December 1996; accepted 10 July 1997
 |
Abstract |
|---|
 Top Abstract 1 Introduction2 Methods3 Results4 DiscussionReferences |
|---|
Objective: The effect of the chronic administration of L-arginine on intimal thickness and the kinetics of smooth muscle cell proliferation in autovein grafts in hypercholesterolemic rabbits were examined. Methods: Male rabbits were fed a 1% cholesterol diet (control group) and a 1% cholesterol diet supplemented by 2.25% L-arginine HCl in drinking water (arginine group). Each group underwent reversed autologous vein bypass grafting of the left common carotid artery using the left external jugular vein. At 2 or 4 weeks after operation, intimal cell proliferation was determined by 5-bromo-2'-deoxyuridine (BrdU) incorporation and intimal thickness of the graft was measured with an ocular cytometer. At 4 weeks after operation, endothelium-dependent responses were examined by isometric tension recording. Results: At 4 weeks after operation, the level of plasma arginine and citrulline are significantly higher in the arginine group (n = 7), compared with the control (n = 7). Intimal thickness in the arginine group (n = 7) was significantly reduced, compared with that of the control (n = 7). At 2 weeks after operation, the BrdU labeling index of the control (n = 5) was significantly higher than that of the arginine group (n = 5). At 4 weeks after operation, ACh caused endothelium-dependent relaxation in the arginine group (n = 4), while in the control (n = 4), ACh did not relax. Conclusions: These results suggest that smooth muscle cell proliferation of the rabbit jugular vein grafts during hypercholesterolemia occurs at an early stage after graft implantation, prior to the development of intimal thickness. Intimal thickness of vein graft during hypercholesterolemia was reduced by chronic administration of dietary L-arginine, by inhibiting smooth muscle cell proliferation. The enhancement of NO production in the blood vessel wall may therefore be useful for preventing late graft failure.
KEYWORDS Nitric oxide; L-arginine; Vein graft; Hypercholesterolemia
|
1 Introduction |
|---|
|
TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
|---|
An autologous vein graft is the most suitable conduit for reconstruction at many sites of arterial occlusive disease [1]. In the early postoperative period after graft replacement, besides technical difficulties, acute platelet thrombosis may frequently lead to graft occlusion [2]. Late graft occlusion tends to be caused by either intimal thickness or a progression of the underlying atherosclerotic vascular disease [3, 4].
Endothelium-derived relaxing factor (EDRF), which is now known as nitric oxide (NO) [5], has recently been shown to be not only a potent vasodilator but also to inhibit leukocyte–endothelial interaction [6, 7], platelet adherence and aggregation [8–10]and vascular smooth muscle proliferation [11].
L-arginine is the precursor for the formation of NO [12, 13]. The administration of L-arginine enhances NO production, which in turn reduces the development of proliferative atherosclerotic lesions [14]and intimal hyperplasia after balloon angioplasty [15]. Recently, Davies et al. [16]demonstrated that L-arginine reduced the degree of intimal thickness in experimental vein grafts.
Hypercholesterolemia is one of the most important risk factors for atherosclerosis [17, 18]and it also accelerates graft failure [19, 20]. We recently demonstrated that hypercholesterolemia accelerated intimal thickness in the rabbit femoral vein grafts [20]; this was due to the enhancement of cell proliferation. However, little information is available regarding the effect of L-arginine on either intimal thickness or smooth muscle cell proliferation induced by hypercholesterolemia. The present experiments were therefore designed to determine whether or not the chronic administration of L-arginine inhibits the intimal thickness of autologous vein grafts and reduces the cholesterol levels in hypercholesterolemic rabbits. In addition, the intimal cell proliferation determined by 5-bromo-2'-deoxyuridine (BrdU) incorporation and the endothelium-dependent responses by isometric tension recording were also examined.
|
2 Methods |
|---|
|
TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
|---|
Male New Zealand White Rabbits (Body weight: 2.5–3.0 kg), which received 1% cholesterol chow (chow contains 1.12% L-arginine) were divided into two groups as follows: The control group received normal drinking water. The arginine group received 2.25% L-arginine (L-arginine, Sigma Chemical, St. Louis, MO) [14]supplementation in their drinking water (2.25 g/100 ml; for an average daily dose of 2 g/kg body weight). The above chow was fed 14 days before operation, and the arginine was administered 7 days before operation and thereafter both were continued until harvest.
Each group underwent a reversed autologous vein bypass grafting of the left common carotid artery with the left external jugular vein [21, 22]. All animals were then killed with an overdose of pentobarbital sodium and the arterial vein bypass grafts were harvested 14 days or 28 days postoperatively.
All animal care complied with the Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals (National Institute of Health, publication No. 85-23, revised 1985).
2.1 Operative procedures
Anesthesia was induced with ketamine hydrochloride (70 mg/kg, intramuscularly, Sigma Chemical, St. Louis, MO) and maintained with pentobarbital sodium (30 mg/kg, intravenously). The operation was performed with an operating microscope (Topcon, Tokyo, Japan) under sterile conditions. After a longitudinal neck incision, the left external jugular vein and the left common carotid artery were exposed. The branches of the jugular vein were ligated and then the vein was excised. After excision, the vein was kept moistened in heparinized (5 units/ml) saline solution. Heparin (200 units/kg) was administered intravenously. The carotid artery was clamped at the proximal and distal ends. A proximal longitudinal arteriotomy was made, and the jugular vein was reversed and anastomosed to the artery in an end-to-side manner by use of a continuous 10-0 monofilament nylon suture. Distal anastomosis was performed in a similar manner. The left common carotid artery was ligated and divided between the two anastomosis with 9-0 silk sutures, and then the wound was closed in layers.
2.2 Blood sample analysis
Blood was obtained from a cannula placed in the middle ear artery at the time of operation and at 2 or 4 weeks after operation before animals were killed under anesthesia. The concentration of the plasma arginine and plasma citrulline, which is a by-product of nitric oxide, was measured by reverse phase high-performance liquid chromatography [23]. The total plasma cholesterol levels were assayed spectrophotometrically using a commercially available kit (Type L Wako Cholesterol; Wako Chemicals, Japan).
In addition, the plasma cholesterol levels were assayed in the normolipidemic rabbits (n = 7).
2.3 Blood pressure measurement
At operation and 4 weeks after operation on harvest, the systolic blood pressure was measured through a cannula placed in the middle ear artery using a pressure transducer connected to a Polygraph 360 monitoring system (NEC Sanei, Tokyo, Japan). All measurements were made under anesthesia conditions.
2.4 Harvest of implanted grafts
At 2 weeks after operation, the rabbits in the control (n = 5) and L-arginine (n = 5) group were sacrificed. At 4 weeks after operation, the rabbits in the control (n = 7) and L-arginine (n = 7) group were sacrificed. BrdU 40 mg/kg (Sigma Chemical, St. Louis, MO) was administrated intravenously one hour before sacrifice. The vein grafts were then exposed and isolated. After heparinization (200 IU/kg intravenously), the vein grafts were perfusion fixed in situ at 100 cm H2O with 4%. paraformaldehyde for 30 min. The perfused autologous vein graft, including anastomosis, was totally removed and immersed in the same fixative overnight at 4°C [20, 24].
2.5 Sample processing and immunohistochemical staining
The middle portion of the harvested graft was used for histological studies. Each sample was paraffin-embedded and cut using a microtome into four micrometer thick sections, which were then mounted on glass slides. For the immunohistological analysis, monoclonal anti-rabbit macrophage, RAM-11 (Dako, Carpinteria, CA), was used [20]. Immunohistochemical staining was done as follows using the avidine–biotin complex (ABC) technique; the deparaffinized sections were treated with 0.3% hydrogen peroxidase in methanol for 30 min at room temperature to inhibit endogenous peroxidase. After washing in phosphate buffered saline (PBS) and incubating with normal rabbit serum, each section was incubated with RAM-11 diluted 1:50 for 2 h. For the avidin–biotin–peroxidase complex, the Histofine SAB-PO mouse immunoglobulin kit was utilized. Visualization of the peroxidase was achieved using the diaminobenzine (DAB) method. Each section was counterstained with hematoxylin–eosin and examined under a transmission light microscope [20].
2.6 BrdU staining and measurement of the labeling index
Each section was deparafinized in a xylene–ethanol series. For DNA denaturation, the sections were first incubated in 2 M HCl for one hour and neutralized with 0.1 M sodium tetraborate, then digested with 0.05% protease (type XXV, Sigma Chemical, St. Louis, MO) for 5 min at 37°C, and rinsed with PBS. After the inhibition of endogenous peroxidase and incubation with normal rabbit serum, the sections were incubated with anti-BrdU monoclonal mouse antibody (1:50, Becton Dickinson Immunocytometry Systems, Mountain View, CA), overnight at 4°C. After rinsing in PBS, the ABC technique was then completed using the Histofine SAB-PO mouse immunoglobulin kit. Peroxidase visualization was achieved by the DAB method and counterstaining was done with hematoxylin–eosin. All cells possessing incorporated BrdU were identified by the presence of brown pigment over the nuclei. BrdU-labeled cells were counted in the intima of each cross section. The BrdU labeling index was expressed as a percentage of the total number of cells scored in the intima [20, 24].
2.7 Measurement of endothelium dependent relaxation [25]
At four weeks after operation, the responses of a pair of rings with and without endothelium taken from control group (n = 4) and arginine group (n = 4) were studied as follows. The jugular vein grafts were sectioned into rings 3 to 4 mm in length. The vessel rings were suspended from stainless steel hooks in an organ bath that contained oxygenated Krebs solution of the following millimolar composition: NaCl 123, KCl 4.7, NaHCO3 15.5, KH2PO4 1.2, MgCl2 1.2, CaCl2 1.25, and D-glucose 11.5, bubbled with 95% O2 and 5% CO2 and maintained at 37°C. The hooks were connected to a force-transducer (strain gauge TB-612T, Nihon Kohden, Japan), and the data of isometric contraction were stored in a Macintosh computer using a data acquisition system (MacLab) with a sampling rate of 17 Hz. During the 30 min equilibration period, the vessel rings were stimulated with 118 mM K+ every 15 min, and the resting load was increased in a stepwise manner to obtain the maximal force development. The resting load for the measurements, thus obtained, was between 200 and 250 mg.
After the resting loads were obtained, the rings were precontracted with the 3x10–7 M norepinephrine, which caused approximately 60% of the maximal contraction induced by 3x10–5 M norepinephrine. At the contraction plateau, increasingly larger doses of acetylcholine (ACh) were added in a cumulative manner (10–9–10–4 M). The force development was expressed as a percentage, while assigning the values the resting load and the steady state contraction induced by 3x10–7 M norepinephrine to be 0% and 100%, respectively.
In order to examine the effects of L-NMMA (L-NG-monomethyl arginine) (10–4 M) on endothelium-dependent responses in the arginine group, the rings (n = 3) with endothelium were incubated with L-NMMA for 30 min. In the presence of L-NMMA, the endothelium-dependent responses to ACh (10–9–10–4 M) were examined.
For relaxations, the effective concentration of vasodilators causing 50% inhibition (ED50) of the contractions to norepinephrine (3x10–7 M) was calculated from each concentration–response curve, and the means of these values were presented as the negative logarithm of the molar concentration.
The following drugs were used. acetylcholine chloride (ACh), 1-norepinephrine bicarbonate (NE) and L-NMMA (L-NG-monomethyl arginine) (all from Sigma Chemical, St. Louis, MO).
2.8 Assessment of intimal thickness
The sections were stained with hematoxylin–eosin and using the elastic van Gieson's method. Intimal thickness was measured with an ocular cytometer placed on the ocular lens of a light microscope at a magnification of 400x. The average intimal thickness of more than eight randomly selected points of each sample was taken as the degree of intimal thickness [26]. The area of the intima and media were also calculated by videomorphometry (Cosmozone IS; Nikon, Tokyo, Japan), and the ratio of the intimal and medial areas was also calculated (intima/media ratio=intimal area/medial area) [27].
2.9 Statistical analysis
Statistical evaluation of the data was made using Student's t-test for unpaired observations. When more than two means were compared, an analysis of variance was used. If the value was statistically significant, Scheffe's test for multiple comparisons was used to identify differences among the groups [28]. A value of p<0.05 was considered to have statistical significance.
|
3 Results |
|---|
|
TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
|---|
All animals survived, and all the grafts were patent at harvest.
3.1 Systemic measurements
The animal body weights at the time of sacrifice were not different between the two groups. At operative day and 4 weeks after, the systolic arterial pressure was comparable in both the control and arginine groups. In addition, at the time of sacrifice, the plasma cholesterol levels were not significantly different between the two groups. However, those cholesterol levels were significantly higher than those of normolipidemic rabbits (n = 7; 1.1±0.6 mmol/l). At the time of sacrifice, the plasma arginine levels and the citrulline levels in the arginine group were significantly higher than those in the control group (Table 1).
|
3.2 Endothelium-dependent responses
Precontracted vein grafts taken from control group (n = 4) did not relax to ACh, whereas those from the arginine group (n = 4), ACh caused endothelium-dependent relaxation in a dose dependent manner. Maximum relaxations were 55.3±12.8% and ED50 (–log M) was 5.3±0.8. Preincubation with 10–4 M L-NMMA completely abolished the endothelium-dependent relaxations (n = 3).
3.3 Progression of intimal thickness
At 2 weeks after operation, the vein grafts in the arginine group showed a reduced degree of intimal thickness compared with that of the control group, although the difference was not significant. The intima/media ratio was also comparable in both groups (Table 2 and Fig. 1).
|
|
At 4 weeks after operation, the vein grafts in both the arginine group and the control group showed a remarkable degree of intimal thickness development in the smooth muscle cells. However, the intimal thickness in the arginine group was significantly reduced compared with that of the control group. The intima/media ratio in the arginine group was also significantly inhibited, compared to that of the control group (Table 3 and Fig. 1).
|
3.4 Immunohistochemical distribution of the foamy macrophages
At 2 weeks after operation, the cross section of the grafts demonstrated thin fibrocellular neointima, and RAM-11 positive foamy macrophages were scattered in the outer layer of the thickened intima in both groups (Fig. 2a and b). Four weeks after implantation, the autologous vein grafts of cholesterol-fed rabbits showed markedly thickened neointima diffusely containing many RAM-11 positive foam cells (Fig. 2d). In contrast, the vein grafts implanted under the hypercholesterolemia with L-arginine administration demonstrated reduced neointima lesion consisting mainly of smooth muscle cells. The RAM-11 positive foamy macrophages were observed scattered in the inner and outer layers of the thickened intima (Fig. 2c).
|
3.5 BrdU incorporation
The BrdU labeling index (LI) at 2 weeks after operation was significantly higher in the control group, compared with that in the arginine group (Table 2).
The number of BrdU positive cells decreased in both groups at 4 weeks after operation. The BrdU LI was slightly higher in the control group, compared with that in the arginine group, although the difference was not significant (Table 3).
|
4 Discussion |
|---|
|
TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
|---|
Late graft failure is usually attributed to graft thrombosis, based on either intimal thickness or a progression of the underlying atherosclerotic vascular disease [3, 4]. The critical relationship between endothelial cells and the development of intimal thickness has been well recognized. Endothelial cells are known to release growth factors and heparin-like compounds, which likely have a major influence on surrounding cells and also help maintain normal vessel wall homeostasis [29–32]. Intimal thickness is the result of complex interactions among platelets, leukocytes and smooth muscle cells, all of which are affected by NO [33, 34]. We and other investigators demonstrated a reduced production of NO in experimental autogenous vein grafts [21, 28, 30, 35, 36]. On the other hand, the enhanced EDRF production reduced the degree of intimal thickness in the vein grafts [37]. Thus, a relationship may therefore exist between NO and intimal thickness in vein grafts [38].
L-arginine is the precursor for the formation of NO [5]. The administration of L-arginine has been shown to reverse defects in NO activity and also reduce the development of proliferative atherosclerotic lesions [14]. Tarry et al. [15]demonstrated that L-arginine supplementation enhances NO production at the site of vascular healing and may reduce intimal thickness after balloon angioplasty. In addition, in the rabbit vein grafts, L-arginine reduced experimental vein graft intimal thickness [16]. The present results demonstrate that the elevation of plasma L-arginine and L-citrulline levels, which is a by-product of NO [39], may thus reflect the increase in NO production. These changes occurred despite the fact that L-arginine supplementation did not affect the serum cholesterol level. These data are similar to previous reports [15, 16]in that L-arginine supplementation enhances the NO production in the endothelium and may thus inhibit the degree of intimal thickness in vein grafts in hypercholesterolemic animal models.
Hypercholesterolemia accelerates both atherosclerosis and graft failure in vein grafts [19]. Several studies thus demonstrated that NO-mediated relaxation is impaired in hypercholesterolemic animals [39, 40]and humans [41]. This reduction of NO activity in associated hypercholesterolemia appears to be caused by a reduced synthesis and/or increased degradation of NO. On the other hand, Cooke et al. [14]showed that long-term L-arginine supplementation in hypercholesterolemic rabbits decreases atherogenesis in the aortic wall with decreased histologic lesion development, a reduced SMC proliferation, and a preservation of the endothelium-dependent relaxation. The results of the present study are similar, in that the treatment of the cholesterol-fed animals with arginine preserved ACh-induced endothelium-dependent relaxations. In addition, these endothelium-dependent relaxations were abolished by L-NMMA. These results demonstrated that the effects of L-arginine on the inhibition in the intimal thickness caused by hypercholesterolemic vein grafts are mediated through the enhancement of NO production.
In the presence of hyperlipidemia, endothelial dysfunction as a result of exposure to agents, such as oxidized low density lipoprotein (LDL) increases monocyte/macrophages adherence, and they migrate beneath the endothelium. The macrophages become large foam cells due to lipid accumulation, then form a fatty streak, the initial lesion of atherosclerosis [42]. Interestingly, the present results demonstrated that in the immunohistochemical distribution of macrophages, the RAM-11 positive foamy macrophages in the arginine group seemed to be reduced in number in the inner and outer layers of the thickened intima without changing the plasma cholesterol level. These results suggest that one of the mechanisms of NO inhibiting in the intimal hyperplasia may modulate monocyte requirement or foam cell lipid accumulation [27].
Zwolak et al. [43]showed that smooth muscle cell (SMC) proliferation in the thickened intima was maximal at one week after grafting. Similarly, Itoh et al. [20]also showed with BrdU incorporation that intimal SMC accelerated to two weeks after implantation, and that this acceleration was enhanced in rabbit femoral vein grafts if hypercholesterolemia was present. The present experiments demonstrated that the BrdU labeling index at 2 weeks after operation was significantly inhibited in the arginine group, compared with that of the control group, although after four weeks the BrdU labeling index was comparable between the two groups. On the other hand, at 2 weeks after operation, the degree of intimal thickness was comparable between the two groups, while at 4 weeks after operation, the degree of intimal hyperplasia in the arginine group significantly reduced compared with that of the control group. These results suggest that SMC proliferation of the jugular vein graft wall in hypercholesterolemic rabbits is rapid at the early stage after graft implantation and the proliferation of intimal cell in vein grafts was accelerated prior to the development of intimal thickness. NO is a potent inhibitor of SMC growth [11, 44]. Therefore, L-arginine inhibited intimal SMC proliferation, thus inhibiting intimal thickness. To our knowledge, the present results demonstrate for the first time that L-arginine supplementation significantly inhibited smooth muscle cell proliferation of the vein grafts.
In conclusion, we demonstrated that the chronic administration of L-arginine, the precursor of NO, inhibited intimal thickness in jugular autogenous vein grafts in hypercholesterolemic rabbits by inhibiting the proliferation of SMC. The enhancement of NO production by the endothelium may thus be beneficial for preventing late graft failure.
Time for primary review 30 days.
|
Acknowledgements |
|---|
We thank Mr. Brian Quinn for reading this manuscript.
|
References |
|---|
|
TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
|---|
- Szilagyi D.E., Hageman J.H., Smith R.F., Elliott J.P., Brown F., Dietz P. Autogenous vein grafting femoropopliteal atherosclerosis. Surgery (1979) 86:836–851.[Web of Science][Medline]
- Bernhard VM. Bypass to popliteal and infrapopliteal arteries. In: Rutherford RB, editor. Vascular Surgery, 3rd edn. Philadelphia: Saunders, 1989;692–704.
- Gunstensen J., Smith R.C., El-Maraghi J.J., Belbeck L. Intimal hyperplasia in autogenous veins used for arterial replacement. Can J Surg (1982) 25:158–161.[Web of Science][Medline]
- Karayannacos P.E., Hostetler J.R., Bond M.G., Kakos G.S., Williams R.A., Kilman J.W., Vasco J.S. Late failure in vein grafts: mediating factors in subendothelial fibromuscular hyperplasia. Ann Surg (1978) 187:183–188.[Web of Science][Medline]
- Palmer R.M.J., Ferrige A.G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature (1987) 327:524–526.[CrossRef][Medline]
- Johnston G., Tsao P.S., Malloy D., Leffer A.M. Cardioprotective effects of acidified sodium nitrite in myocardial ischemia with reperfusion. J Pharmacol Exp Ther (1990) 252:35–41.
[Abstract/Free Full Text] - Kubes P., Suzuki M., Granger D.M. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA (1991) 88:4651–4655.
[Abstract/Free Full Text] - Radomski M.W., Palmer R.M.J., Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide, and prostacyclin in platelets. Br J Pharmacol (1987) 92:181–187.[Web of Science][Medline]
- Stamler J.S., Mendelsohn M.E., Amarante P., Smick D., Andon N., Davies P.F., Cooke J.P., Loscalzo J. N-acetylcysteine potenciates platelet inhibition by endothelium-derived relaxing factor. Circ Res (1989) 65:789–795.
[Abstract/Free Full Text] - Radomski M.W., Palmer R.M.J., Moncada S. An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Natl Acad Sci USA (1990) 87:5193–5197.
[Abstract/Free Full Text] - Garg U.C., Hassid A. Nitric-oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest (1989) 83:1774–1777.[Web of Science][Medline]
- Palmer R.M.J., Ashton D.S., Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature (1988) 333:664–666.[CrossRef][Medline]
- Palmer R.M.J., Rees D.D., Ashton D.S., Moncada S. L-arginine is the precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Common (1988) 153:1251–1256.[CrossRef][Web of Science][Medline]
- Cooke J.P., Singer A.H., Tsao P.S., Zera P., Rowan R.A., Billingham M.E. Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit. J Clin Invest (1992) 90:1168–1172.[Web of Science][Medline]
- Tarry W.C., Makhoul R.G. L-arginine improves endothelium-dependent vasorelaxation and reduces intimal hyperplasia after balloon angioplasty. Arterioscler Thromb (1994) 14:938–943.
[Abstract/Free Full Text] - Davies M.G., Kim J.H., Dalen H., Makhoul R.G., Svendsen E., Hagen P.O. Reduction of experimental vein graft intimal hyperplasia and preservation of nitric oxide-mediated relaxation by the nitric oxide precursor L-arginine. Surgery (1994) 116:557–568.[Web of Science][Medline]
- Ross R. The pathogenesis of atherosclerosis. N Engl J Med (1986) 314:488–500.[Web of Science][Medline]
- Komori K., Shimokawa H., Vanhoutte P.M. Hypercholesterolemia impairs endothelium-dependent relaxations to aggregating platelets in porcine iliac arteries. J Vasc Surg (1989) 10:318–325.[CrossRef][Web of Science][Medline]
- Campeau L., Enjalbert M., Lesperance J., Bourassa M.G., Kwiterovich P., Wacholder S., Sniderman A. The relation of risk factors to the development of atherosclerosis in saphenous vein bypass grafts and the progression of disease in the native circulation. A study 10 years after aortocoronary bypass surgery. N Engl J Med (1984) 311:1329–1332.[Abstract]
- Itoh H., Komori K., Funahashi S., Okadome K., Sugimachi K. Intimal hyperplasia of experimental autologous vein graft in hyperlipidemic rabbits with poor distal runoff. Atherosclerosis (1994) 110:259–270.[CrossRef][Web of Science][Medline]
- Komori K., Gloviczki P., Bourchier R.G., Miller V.M., Vanhoutte P.M. Endothelium-dependent vasorelaxations in response to aggregating platelets are impaired in reversed vein graft. J Vasc Surg (1990) 12:139–147.[CrossRef][Web of Science][Medline]
- Komori K., Schini V.B., Gloviczki P., Bourchier R.G., Vanhoutte P.M. The impairment of endothelium dependent relaxations in reversed vein grafts is associated with a reduced production of cyclic GMP. J Vasc Surg (1991) 14:67–75.[CrossRef][Web of Science][Medline]
- Moore S., Stein H.W. Chromatography of amino acids on sulfonated polystyrene resions. J Biol Chem (1951) 192:663–681.
[Free Full Text] - Yamaura S., Okadome K., Onohara T., Komori K., Sugimachi K. Blood flow and kinetics of smooth muscle cell proliferation in canine autologous vein grafts: In vivo bromodeoxyuridine incorporation. J Surg Res (1994) 56:155–161.[CrossRef][Web of Science][Medline]
- Eguchi D., Nishimura J., Kobayashi S., Komori K., Sugimachi K., Kanaide K. Mechanism of contraction induced by bradykinin in rabbit saphenous vein. Br J Pharmac (1997) 120:371–378.[CrossRef][Web of Science][Medline]
- Morinaga K., Eguchi H., Miyazaki T., Okadome K., Sugimachi K. Development and regression of intimal thickening of arterially transplanted autologous vein grafts in dogs. J Vasc Surg (1987) 5:719–730.[CrossRef][Web of Science][Medline]
- Cayatte A.J., Palacino J.J., Horten K., Coben R.A. Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits. Arterioscler Thromb (1994) 14:753–759.
[Abstract/Free Full Text] - Ishii T., Okadome K., Komori K., Odashiro T., Sugimachi K. Natural course of endothelium-dependent and -independent responses in autogenous femoral veins grafted into the arterial circulation of the dog. Circ Res (1993) 72:1004–1010.
[Abstract/Free Full Text] - Gajdusek C., DiCorleto P., Ross R., Schwartz S.M. An endothelial cell-derived growth factor. J Cell Biol (1980) 85:472–476.
- Castellot J.J., Addonizio M.L., Rosenberg R.D., Karnovsky M.J. Cultured endothelial cells produce a heparinlike inhibitor of smooth muscle cell growth. J Cell Biol (1981) 90:372–379.
[Abstract/Free Full Text] - DiCorleto P.E., Bowen-Pope D.F. Cultured endothelial cells produce a platelet-derived growth factor-like protein. Proc Natl Acad Sci USA (1983) 80:1919–1923.
[Abstract/Free Full Text] - Castellot J.J., Faveau L.V., Karnovsky M.J., Rosenberg R.D. Inhibition of vascular smooth muscle cell growth by endothelial cell-derived heparin. J Biol Chem (1982) 257:11256–11260.
[Abstract/Free Full Text] - Cole C.W., Hagen P.O., Lucas J.F., Mikat E.M., O'Malley M.K., Radic Z.S., Makhoul R.G., McCann R.L. Association of polymorphonuclear leukocytes with sites of aortic catheter-induced injury in rabbits. Atherosclerosis (1987) 67:229–236.[CrossRef][Web of Science][Medline]
- Cole C.W., Makhoul R.G., McCann R.L., O'Malley M.K., Hagen P.O. A neutrophil derived factor(s) stimulates [3H]-thymidine incorporation by vascular smooth muscle cells in vitro. Clin Invest Med (1988) 11:62–67.[Web of Science][Medline]
- Miller V.M., Reigel M.M., Hollier J.H., Vanhoutte P.M. Endothelium-dependent responses in autogenous femoral veins grafted into the arterial circulation. J Clin Invest (1987) 80:1350–1357.[Web of Science][Medline]
- Cross K.S., El-Sanadiki M.N., Murray J.J., Mikat E.M., McCann R.L., Hagen P.O. Functional abnormalities of experimental autogenous vein grafts neoendothelium. Ann Surg (1988) 208:631–638.[Web of Science][Medline]
- Komori K., Ishii T., Odashiro T., Itoh H., Mawatari K., Okadome K., Sugimachi K. Eicosapentanoic acid reduces the intimal thickening of autogenous vein grafts and enhances endothelium-derived relaxing factor. J Surg Res (1995) 59:747–753.[CrossRef][Web of Science][Medline]
- Komori K., Okadome K., Sugimachi K. Endothelium-derived relaxing factor and vein grafts. Br J Surg (1991) 78:1027–1030.[CrossRef][Web of Science][Medline]
- Frieman R.C., Mitchell G.G., Heistad D.D., Armstrong M.L., Harrison D.G. Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primatres. Circ Res (1986) 58:783–789.
[Abstract/Free Full Text] - Komori K., Shimokawa H., Vanhoutte P.M. Hypercholesterolemia impairs endothelium-dependent relaxations to aggregating platelets in porcine iliac arteries. J Vasc Surg (1989) 10:318–325.[CrossRef][Web of Science][Medline]
- Ludmer P.L., Selwyn A.P., Shook T.L., Wayne R.R., Mudge G.H., Alexander R.W., Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Eng J Med (1986) 315:1046–1050.[Abstract]
- Ross R, The pathogenesis of atherosclerosis: Aperspective for 1990s. Nature 1993;362:801-809.
- Zwolak R.M., Adams M.C., Clowes A.W. Kinetics of vein graft hyperplasia: Association with tangenital stress. J Vasc Surg (1987) 5:126–136.[CrossRef][Web of Science][Medline]
- Scott-Burden T., Vanhoutte P.M. The endothelium as a regulator of vascular smooth muscle proliferation. Circulation (1993) 87(Suppl_V):51–57.[Web of Science]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Yamaoka, Y. Yonemitsu, K. Komori, H. Baba, T. Matsumoto, T. Onohara, and Y. Maehara Ex vivo electroporation as a potent new strategy for nonviral gene transfer into autologous vein grafts Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1865 - H1872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Kown, M. A. Lijkwan, C. L. Jahncke, S. Murata, J. B. Rothbard, and R. C. Robbins L-arginine polymers enhance coronary flow and reduce oxidative stress following cardiac transplantation in rats J. Thorac. Cardiovasc. Surg., October 1, 2003; 126(4): 1065 - 1070. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shoji, Y. Yonemitsu, K. Komori, M. Tanii, H. Itoh, S. Sata, H. Shimokawa, M. Hasegawa, K. Sueishi, and Y. Maehara Intramuscular gene transfer of FGF-2 attenuates endothelial dysfunction and inhibits intimal hyperplasia of vein grafts in poor-runoff limbs of rabbit Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H173 - H182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Kown, A. Yamaguchi, C. L. Jahncke, D. Miniati, S. Murata, J. Grunenfelder, M. L. Koransky, J. B. Rothbard, and R. C. Robbins L-arginine polymers inhibit the development of vein graft neointimal hyperplasia J. Thorac. Cardiovasc. Surg., May 1, 2001; 121(5): 971 - 980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Oomen, M. J. van Erk, E. J. M. Feskens, F. J. Kok, and D. Kromhout Arginine Intake and Risk of Coronary Heart Disease Mortality in Elderly Men Arterioscler Thromb Vasc Biol, September 1, 2000; 20(9): 2134 - 2139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Fike, M. R. Kaplowitz, L. A. Rehorst-Paea, and L. D. Nelin L-Arginine increases nitric oxide production in isolated lungs of chronically hypoxic newborn pigs J Appl Physiol, May 1, 2000; 88(5): 1797 - 1803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C Ray, M. E Landis, and V. M Miller Effects of dietary l-arginine on the reactivity of canine coronary arteries Vascular Medicine, November 1, 1999; 4(4): 211 - 217. [Abstract] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||